Post-translational modification (PTM) of the lysines and other residues in the N-terminal tails of histones are known to have profound effects on the structure and function of chromatin, perhaps most notably on the regulation of gene expression. One of these 'epigenetic' histone modifications, the PTM lysine acetylation is generally associated with gene activation. Epigenetic regulation of gene expression plays significant roles in normal development, as well as in diseases, including cancer, neurodegeneration and metabolic disease. The 'perception' of the chromatin acetylation state is mediated by proteins that contain a type of modular epigenetic reader domain, a bromodomain. The human bromodomains, 61 different domains present in 46 distinct proteins, are the principal known class of acetyllysine readers. The bromodomains, particular a subclass known as the BET family are implicated in various disease states including cancer, inflammation, type II diabetes, atherosclerosis and viral infections. Investigation of the biological roles and disease connections of the BET family has been aided tremendously by the development of high affinity inhibitors, sometimes termed chemical probes, which also show promise as possible therapeutic agents for cancer and other diseases. The development of probes for many of the non-BET bromodomains, however, has lagged and to some extent this may be due to deficiencies in the available assay systems, which can on the one hand be simple to use and relative artefact free, albeit not very quantitative (thermal melt/shift, aka Differential Scanning Fluorimetry) and on the other hand, highly sensitive and quantitative assays (AlphaScreen) that are expensive, relative difficult to implement and prone to numerous 'false hit' artefact when screening compound libraries. We propose to address this problem by developing a suite of simple to perform, quantitative but, inexpensive fluorescence polarization (FP) assays, based on fluorophor-conjugated bromodomain inhibitor compounds. Our goal is for these assays to be broadly applicable to the 61 human bromodomains. In order to accomplish that efficiently, we propose to screen for 'promiscuous' bromodomain inhibitors, so that relatively few of these, in fluorophor-conjugated form, will be needed to allow convenient assay of the entire set of human bromodomains. We argue, and have some preliminary evidence to suggest, that phenolic plant natural products, particularly the chalcones and flavones may be relatively rich in suitable inhibitor compounds. Hits from screening these and other compounds classes, along with already developed probe compounds will be coupled to fluorophors to produce FP probes and these will be used to develop the assays.